MOLECULAR PHARMACOLOGICAL STUDIES ON MECHANISMS ASSOCIATED WITH NEUROMODULATION BY GLUTATHIONE

体外添加谷胱甘肽对大鼠突触体中[^3H]-谷氨酸（Glu）和[^3H] γ -氨基丁酸（GABA）的吸收没有显著影响，其浓度范围高达1mm。这些结果表明，谷胱甘肽在Glu和GABA进入神经元和/或胶质细胞的运输系统中没有生理作用。另一方面，在先前注射谷胱甘肽消耗物2-环己烯- 1后，亚惊痫性低剂量的kainic酸（KA）腹腔注射显著增强了脑内源性谷胱甘肽含量降低的小鼠海马中转录因子激活蛋白- 1 （APl）的DNA结合活性，而对先前单独注射生理盐水的小鼠没有明显影响。然而，消耗剂对小鼠海马中n -甲基- d -天冬氨酸（NMDA）对APl DNA结合的增强作用没有显著调节。本文引用的数据提出了一种可能性，即内源性谷胱甘肽可能在小鼠海马中通过KA而不是NMDA受体到核AP1的信号级联机制中发挥关键作用。此外，利用谷胱甘肽固定的亲和树脂柱层析技术，从猪脑中分离到了不同分子量的膜蛋白。

In vitro addition of glutathione did not significantly affect uptake of [^3H]-glutamic (Glu) and [^3H] gamma-aminobutyrrc (GABA) acids into rat synaptosomal fractions at a concentration range of up to 1 mM These results suggest that glutathione plays no physiological role in transport systems of Glu and GABA into neuronal and/or glial cells. On the other hand, an intraperitoneal injection of kainic acid (KA) at a subconvulsive low dose markedly potentiated DNA binding ac tivity of the transcription factor activator protein-l (APl) in the hippocampus of mice with reduced contents of brain endogenous gluthatione following a previous injection of the glutathione depletor 2-cyclohexen-l-one, without markedly affecting that in animals previously injected with saline alone. However, the depletor did not significantly modulate the potentiation of APl DNA binding by the administration of N-methyl-D-aspartic acid (NMDA) in murine hippocampus. The data cited here raise the possibility that endogenous glutathione may play a critical role in mechanisms underlying signaling cascade through KA, but not NMDA,receptors to nuclear AP1 in murine hippocampus. Moreover, several membrane proteins with different molecular weights were isolated from porcine brains following column chromatography using affinity resins immobilized with glutathione.